The White House Conference on Aging focused much attention on the nutritional needs of the elderly, citing impairment of taste and smell as major factors leading to an inadequate diet. Research done during the course of this grant indicates substantial age-related loss in food recognition and smell discrimination in the aged with more moderate losses in taste. These decrements with age are not uniform across stimuli, however. For example, the taste losses for the amino acids L-glutamic acid and L-aspartic acid are greater than for the amino acids L-lysine and L-leucine. This grant proposes a series of experiments to explore the mechanisms responsible for these nonuniform decrements. First, a group of diuretics will be applied to the tongue, impregnated in filter paper, to follow up on the exceptionally important findings described in the progress report that specific ion pathways are involved in taste perception. Specific modes of ion transport will be exhaustively delineated using 1) amiloride, a Na+ channel blocker, 2) the loop diuretic bumetanide, an inhibitor of Na+ K+ 2Cl- contransport, 3) other loop diuretics, furosemide and ethacrynic acid, and 4) mixtures of these specific inhibitors with the aim in view of studying kinetic relations. Second, a simple standardized test will be developed to evaluate taste and smell changes with age. The test will also be used to determine the degree to which chemosensory losses are related to medications taken by the elderly. Third, the nonuniform loss in discriminability among pyrazines with age will be further explored. Pyrazines, the constituents of many foods, will be cross-adapted to investigate whether they use similar receptor sites. The patterns of cross-adaptation will be analyzed by multidimensional scaling procedures and the resultant spaces will be interpreted with techniques used in quantitative drug design. Physical properties such as sigma values and partition coefficients will be examined to predict whether noncovalent bonding is involved in the perception of odor. Finally, specific formulas for addition of commercial odorants to foods will be developed for practical handling of olfactory losses in elderly person.